A Study of JNJ-75229414 for Metastatic Castration-resistant Prostate Cancer Participants
- Conditions
- Prostatic Neoplasms
- Interventions
- Drug: JNJ-75229414Drug: Bridging Therapy
- Registration Number
- NCT05022849
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to determine recommended Phase 2 dose (RP2D) regimen(s) of JNJ-75229414 in Part 1 (Dose Escalation and to determine safety at the RP2D regimen(s) in Part 2 (Dose Expansion).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 15
- Histology: Metastatic CRPC (mCRPC) with histologic confirmation of adenocarcinoma. Metastatic CRPC with neuroendocrine features or mixed histology is excluded
- Prior Therapy: Prior treatment with at least 1 prior novel androgen receptor AR-targeted therapy (that is, abiraterone acetate, apalutamide, enzalutamide, darolutamide), or at least 1 prior chemotherapy (example, docetaxel)
- Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 or 1
- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or detectable prostate-specific antigen (PSA) levels based on local laboratory results
- Fertile participants must use a condom with spermicide during any sexual contact with a woman of childbearing potential, including pregnant women, from the time of signing the ICF until 1 year after receiving a JNJ-75229414 infusion. Vasectomized participants must agree to use a condom to protect any sexual partner from exposure to semen for 1 year after receiving the last dose of study drug. Contraceptive (birth control) use should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies
- Prior Grade 4 Cytokine release syndrome (CRS) or Grade 3 or Grade 4 neurotoxicity related to any T cell redirection (Bispecific cluster of differentiation [CD 3])
- Prior Kallikrein 2 (KLK2)-targeted therapy
- Prior chimeric antigen receptor T cell (CAR-T) therapy
- Receiving systemic treatment less than or equal to (<=) 6 months prior to signing informed consent) for any invasive malignancy other than prostate cancer unless approved by the sponsor. Bisphosphonates initiated greater than or equal to (>=) 6 weeks prior signing informed consent are allowed
- Less than 2 weeks between last administration anti-androgen agents (example, abiraterone or enzalutamide), poly adenosine diphosphate-ribose polymerase (PARP) inhibitors (example, olaparib) or radiotherapy, and less than 3 weeks between last administration of cytotoxic chemotherapy (example, docetaxel), radionuclides (example, radium-223, lutetium-177-Prostate-specific membrane antigen [PSMA]-617) or an investigational agent, and apheresis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1: Dose Escalation Bridging Therapy Participants will receive a conditioning regimen of cyclophosphamide and fludarabine intravenously (IV) followed by JNJ-75229414 IV infusion escalated sequentially with a targeted dose consistent with the dose required by the cohort being enrolled to determine recommended Phase 2 dose (RP2D) regimen(s). Additional, intermediate dose levels may be implemented based on the review of all available data including, but not limited to, safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) by the study evaluation team (SET). Participants may receive bridging therapy (anti-androgen receptor agents \[example, abiraterone, enzalutamide\] and radiotherapy, or chemotherapy \[example, docetaxel\]) if clinically indicated to maintain disease stability. Part 1: Dose Escalation JNJ-75229414 Participants will receive a conditioning regimen of cyclophosphamide and fludarabine intravenously (IV) followed by JNJ-75229414 IV infusion escalated sequentially with a targeted dose consistent with the dose required by the cohort being enrolled to determine recommended Phase 2 dose (RP2D) regimen(s). Additional, intermediate dose levels may be implemented based on the review of all available data including, but not limited to, safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) by the study evaluation team (SET). Participants may receive bridging therapy (anti-androgen receptor agents \[example, abiraterone, enzalutamide\] and radiotherapy, or chemotherapy \[example, docetaxel\]) if clinically indicated to maintain disease stability. Part 2: Dose Expansion JNJ-75229414 Participants will receive JNJ-75229414 for each RP2D regimen determined in Part 1. Part 2: Dose Expansion Bridging Therapy Participants will receive JNJ-75229414 for each RP2D regimen determined in Part 1.
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs) Up to 15 years 9 months An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study.
Number of Participants with AEs by Severity Up to 15 years 9 months Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Part 1: Number of Participants with Dose-limiting Toxicity (DLT) Up to 28 days Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
- Secondary Outcome Measures
Name Time Method Maximum Observe Plasma Concentration (Cmax) of JNJ-75229414 Up to 15 years 9 months Cmax is the maximum observed plasma concentration of JNJ-75229414.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-75229414 Up to 15 years 9 months Tmax is the actual sampling time to reach maximum observed plasma concentration of JNJ-75229414.
Area Under Plasma Concentration Versus Time Curve from Time Zero to t Time (AUC[0-t]) of JNJ-75229414 Up to 15 years 9 months AUC(0-t) is the area under the plasma concentration versus time curve from time zero to 't' time.
Peripheral T Cell Expansion and Persistence via Monitoring Chimeric Antigen Receptor T (CAR-T) Positive Cell Counts Up to 15 years 9 months Peripheral T cell expansion and persistence via monitoring CAR-T positive cell counts will be reported.
Number of Participants With Presence of Anti-JNJ-75229414 Antibodies Up to 15 years 9 months Number of participants with antibodies to JNJ-75229414 will be reported.
Overall Response Rate (ORR) Up to 15 years 9 months ORR is defined as the percentage of participants who achieve a confirmed best overall response of Complete Response (CR) or Partial Response (PR) evaluated by an independent local radiology review based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Prostate Cancer Working Group 3 (PCWG3) criteria will be used to assess progressive bone metastases.
Disease Control Rate (DCR) Up to 15 years 9 months DCR is defined as the sum of CR, PR, and stable disease (SD).
Duration of Response (DoR) Up to 15 years 9 months DoR is defined as the time from the date of first documented responses until date of documented progression or death whichever comes first.
Time to response (TTR) Up to 15 years 9 months TTR defined as the time from the date of first dose of study drug to the date of first documented response.
Peripheral Blood Quantitation of Vesicular Stomatitis Virus G glycoprotein (VSV-G) Copy Numbers Up to 15 years 9 months Peripheral blood quantitation of VSV-G copy numbers will be reported.
Trial Locations
- Locations (8)
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
City of Hope Cancer Center
🇺🇸Duarte, California, United States
University of Utah Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
University Of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States